Work

Expression of α4β7 Integrin on Memory CD8+ T-Cells Is Increased in Patients at Presentation of Acute Intestinal Graft-Vs-Host Disease

Year: 2012

Type: article

Abstract: Acute intestinal graft-vs.-host disease (GVHD) remains a major source of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). α4β7 integrin is a cell surface molecule thought to mediate specific lymphocyte trafficking to intestinal tissue. Our previous work suggested that upregulation of α4β7 integrin expression on memory CD4+ and CD8+ peripheral blood T-cells after HCT correlated with the future development of intestinal GVHD. In this analysis, peripheral blood mononuclear cells were collected from patients at the time of presentation of symptoms of GVHD prior to the initiation of systemic corticosteroids. In total, 27 patient samples were collected prospectively after HCT, which were then retrospectively divided into 3 cohorts: GUT (intestinal GVHD, n = 11), SKIN (cutaneous GVHD, n = 9), and NONE (suggestive symptoms but negative evaluation for GVHD, n = 7). Sample collection ranged from day +23 to day +194 after HCT and was based on symptoms or signs suggestive of GVHD. One patient developed GVHD after donor leukocyte infusion (DLI). There were no significant differences in baseline characteristics between the groups. Analysis by flow cytometry showed that GUT patients had a significantly higher percentage of α4β7 integrin expressing memory (defined by CD45RO+) peripheral blood CD8+ T-cells (median 7.7%, range 0.5%-28.1%) compared to the SKIN group (2.1%, 0%-3.1%, p = 0.03), the NONE group (1%, 0.2%-2.2%, p = 0.02), or the SKIN and NONE groups combined into one NON-GUT (n = 16) group (1.6%, 0%-3.1%, p = 0.01). Time of sample collection after HCT had no effect on the expression of α4β7 integrin. These results add to the evidence that upregulation of α4β7 integrin on memory CD8+ T-cells may be involved in lymphocyte trafficking in acute intestinal GVHD and increased expression may be a potential biomarker. More importantly, α4β7 integrin may represent a novel target of treatment and prophylaxis of acute intestinal GVHD after HCT with specific monoclonal antibodies already in development for the treatment of inflammatory bowel disease. Analysis with a larger number of samples is planned to confirm these results.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2011.12.053